[Show abstract][Hide abstract]ABSTRACT: Amperometric glucose oxidase/hydrogen peroxide sensors were inserted subcutaneously into the neck of normal and diabetic dogs (n = 10), to elucidate the conditions for stable long-term functioning. Their output current was observed in parallel with measurements of plasma glucose concentrations and their function was checked by means of induced alterations in glycaemia. After between 14 and 96 h the experiments were terminated due to losses in the apparent sensitivity of implanted sensors and/or increasing oscillations following stable measurements. This was accompanied by an inflammatory reaction which was analysed on the basis of the clinical picture and histology. In most cases there was a bacterial ingrowth from the normal skin flora of dogs. The inflammatory exsudate contained only 23 +/- 17% of the simultaneous steady state plasma glucose concentration, which was significantly different from the glucose level in the fluid obtained from non-irritate subcutaneous tissue (95 +/- 12%, separate set of experiments). The in vitro calibration of sensors exhibited essentially comparable sensitivities before and after the in vivo application. No differences in reported findings related to the biomaterials used (polyurethane versus cellulose acetate), the presence of diabetes, the history of individual electrodes and the effective duration of a given experiment were discernible. We conclude that the functional bioinstability of subcutaneous glucose sensors is largely due to the inflammatory tissue reaction which alters the effective glucose concentration within the measuring compartment of the electrodes; these drawbacks may be overcome by further miniaturization including implantable telemetric devices allowing the closure of the skin.
Article · Feb 1992 · Journal of Biomedical Engineering
[Show abstract][Hide abstract]ABSTRACT: This study was aimed at validating the in vitro estimated response characteristics of implanted glucose oxidase/H2O2 electrodes with respect to their in vivo function. Monoexponential non-linear regression analysis of sensor current vs. time curves in response to square alterations in glucose concentration gave response times T95 of between 1 and 5 min. Non-primed glucose infusions were applied to dogs with these electrodes implanted subcutaneously. The simultaneously monitored in vivo data were subjected to non-linear regression analysis. The time constants T of increases or decreases after starting or ending the glucose load were (mean +/- SEM) 53 +/- 10 and 26 +/- 4 min (significant difference, p less than 0.05) in sensor current, 28 +/- 8 and 15 +/- 2 min (NS) in whole blood, and 26 +/- 5 and 18 +/- 2 min (NS) in plasma. The in vivo kinetic patterns of sensors were not related to their in vitro response times. Non-linear regression analysis of in vitro responses of glucose sensors under clearly defined conditions is recommended as a basis for further studies. The physiological delay in the subcutaneous glucose system needs more attention in this field of research.
Article · Sep 1991 · The International journal of artificial organs
[Show abstract][Hide abstract]ABSTRACT: An enzyme electrode (GOD, Pt-Ag/AgCl) is introduced for amperometric measurement of the intracorporal glucose concentration in the subcutaneous tissue. Changes of the glucose concentration in the peripheral blood (PG) were induced by glucose- respectively insulin-infusion in healthy dogs. PG was compared with values found by out means of a sensor implanted in the necks of the dogs (SG). The regression equation SG = 0.81 PG - 1.39 was calculated by analysing 62 steady state levels. The regression delta SG = 0.83 delta PG + 0.22 submitted for the deviation of the normoglycemic base-level. A sensibility loss of the sensor of about 10% appears after an implantation duration of 7.5 hours in medium. Conclusions for the further development of the sensors follows especially with the in vivo functions (biocompatibility, diminution, sterilisation).
Article · Feb 1990 · Zeitschrift für experimentelle Chirurgie, Transplantation, und künstliche Organe: Organ der Sektion Experimentelle Chirurgie der Gesellschaft für Chirurgie der DDR
[Show abstract][Hide abstract]ABSTRACT: The subcutaneous tissue is generally considered as a potential site for the monitoring of intracorporal glucose concentration by means of implanted sensors. We studied the suitability of using the resulting signal from the interstitial glucose concentration as an input in a feedback-controlled system for insulin administration. Miniaturized glucose electrodes (amperometric glucose oxidase sensors for the measurement of hydrogen peroxide) were implanted in insulin-dependent diabetic dogs. The output of these sensors was fed into the controller of a bedside-type artificial B cell. Insulin was infused by the device intravenously on the basis of a proportional-differential algorithm. The glucose patterns were compared to identical experiments where feedback control was accomplished on the basis of paracorporal blood glucose measurement using the same algorithm. Normoglycaemia was restored and maintained in both sets of experiments and oral glucose loads were well compensated for. It is concluded that the apparent subcutaneous glucose concentration is appropriate as an input signal for an artificial B cell.
[Show abstract][Hide abstract]ABSTRACT: In realizing the continuous measurement of pO2 and glucose concentration in the subcutaneous tissue, miniaturized electrochemical oxygen- and enzyme glucose sensors, based on modified Clark-type electrodes for transient implantation, were developed and investigated. The electrodes were prepared by means of sequential dipping procedures in glucose oxidase and in different polymer solutions at well-defined environmental conditions in an incubator. By means of combining a hydrophobic membrane with a glucose permeable area and a hydrophilic membrane in the case of the glucose sensor, linearity of the glucose dependent electrode signal up to greater than 20 mmol/l could be achieved. After subcutaneous implantation in the neck of dogs, the enzyme sensor is able to follow glucose profiles in the normo- and in the hyperglycaemic range, e.g. as caused by oral glucose loads. Looking for the difference in sensitivity of the enzyme sensor measured in vitro and calculated from in vivo data, the influence of potential nonspecific, interfering substances in vivo such as urea, amino acids, electrolytes, and albumin was estimated.
[Show abstract][Hide abstract]ABSTRACT: The long-term function of glucose sensors under in-vivo conditions is the first prerequisite in the development of glucose-controlled insulin infusion systems. Amperometric enzyme glucose sensors measuring H2O2 from the enzymatic glucose oxidation are defeated to certain poisoning effects of the electrochemical system and to alterations of the diffusional properties, both resulting in unpredictable changes of the sensor signal. To interpret the signal of subcutaneously implanted sensors after reaching a certain balance of the altering processes, the wick-technique has been established as an independent reference method applicable in the interstitial fluid. Based on the comparison of the wick-glucose concentration and the circulating plasma glucose concentration the in vivo-calibration of the sensor current according to plasma glucose concentration is proven.
Article · Feb 1988 · Hormone and metabolic research. Supplement series
[Show abstract][Hide abstract]ABSTRACT: Employing saline-impregnated cotton threads, an implanted-wick technique was adopted in dogs to obtain specimen from the subcutaneous interstitial compartment in order to estimate its glucose concentration. By measuring the protein, potassium and haemoglobin contents, the centrifuged wick fluid was shown to contain the interstitial concentration of solutes after an equilibration time of approximately 15 min. In normal and in diabetic animals the steady state subcutaneous glucose concentration was almost identical to the circulating glucose level when ranged between 2 and 25 mmol/l. Slow alterations in the circulating glucose profile such as those which appear during an oral glucose tolerance test are closely mirrored by the respective levels in the wick fluid. Fast alterations, however, show deviations. The wick-based glucose levels are well paralleled by the current of Clark type glucose oxidase sensors implanted at the same site. Since, on the basis of in vitro calibrations the sensor outputs have only indicated apparent tissue glucose concentrations of between 70 and 90% of glycaemia, another reference is needed for calibration. Under steady state conditions, the wick method, and on this basis in routine measurements the blood glucose concentration, may be recommended as a reference of implanted sensors which can otherwise not be calibrated in situ.